To our knowledge, this is the first study in Kuwait to provide detailed information on the nutritional status of children and adolescents with CD and related risk factors. Malnutrition, presented as growth stunting, was present in 30% of our study participants with CD and low BMI for age was present in 20.8%. Moreover, few CD cases were identified to have both growth stunting and wasting (5.2%). The same findings were reported by several investigators, such as Dehbozorgi et al., who showed that 31% of Irani CD children had low body weight and 29% had low BMI for age.[16] Also, Setavand et al. found that the prevalence of short stature among 361 children with CD was 18.3% according to CDC criteria and 10% according to WHO criteria; and 20–30% were malnourished with low BMI for age. [17]
The prevalence of growth stunting found in our study was much higher than that in Iran; however, lower than previously reported in Kuwait (72%) by Al-Qabandi 6] Interestingly, the prevalence of growth stunting reported in the Kuwait National Nutrition Survey data for school-aged children in 2019 was 3.70%.[18] None of the healthy controls in our study were growth stunted. CD is prevalent among children with short stature, and the risk of CD in patients with isolated stunted growth or short stature has been estimated to be between 10–40[19] Among 300 children with short stature, Masood et al. found CD in 40%.[20] Stunting is usually a form of long-term malnutrition accompanied by nutrient deficiencies, chronic infection, or disease. Growth failure, short stature, and stunting have been reported as the most common extraintestinal features of CD, originating from the malabsorption of nutrients. However, the pathogenesis of CD-associated short stature remains unclear. Several proposed mechanisms have been considered, including nutrient deficiency, resistance to growth hormones, and low levels of IGF-1. These children usually present with a reduction in IGF-1, IGF-2, insulin-like growth factor binding protein 3 (IGFBP-3), an increase in IGFBP-2 and IGFBP-1 levels, and a blunted GH response to pharmacological stimuli.[19] A significant inverse association was found between the duration of gluten exposure and IGF-1 levels; a significant reduction in IGF-1 levels was observed after prolonged gluten exposure before growth failure. [19] Withdrawal of gluten from the diet is frequently associated with a marked improvement in linear growth within two years.[21]
Growth stunting in childhood has been shown to be associated with impaired fat oxidation, which is proposed as a mechanism mediating obesity in at-risk populations.[22] This double burden of malnutrition increases the risks of mortality, morbidity, and poor cognitive development. Our data showed that growth stunting was concurrent with being overweight and obesity in 3.9% of CD cases. This phenomenon is also observed to a lesser degree among non-celiac school-aged children in Kuwait in boys but not in girls.[18] Overweight and stunting have been found in countries in transition such as rural Mexico, Peru, Russia, Brazil, South Africa, and China.[23–26] In these countries, poor diet quality is typically low in animal protein, high in simple carbohydrates, and low in fat and micronutrients, which may inhibit linear growth, while allowing for fat deposition and obesity.[27] In addition to poor dietary choices, fetal and infant undernutrition, especially during the first thousand days of life, recurrent or chronic infections, and malabsorption conditions, such as CD, modulate the child’s nutritional status, compromising growth. [28]
Among our CD group, 45% had a normal BMI, whereas overweight and obesity was found in 6.5% and 27.3% respectively. Our figures are not different from those previously reported at the nationwide level among children in Kuwait, when levels of overweight and obesity in school aged children were found to be 20.19% and 28.39%, respectively.[29] There are several explanations for overweight and obesity in children with CD, however, few have a well-established association with CD.[30, 31] An increased sense of well-being following treatment may increase both food intake and daily activity. Alterations in diet due to dietary restrictions and close nutritional surveillance can affect the weight and BMI of patients with CD. Overweight and obesity are becoming more common in patients with CD than previously reported.
More than 60% of our CD patients were compliant with GFD. Those had a trend for higher percent fat mass (27.9 (8.98) vs. 23.20 (8.79), p = .089) and lower % fat-free mass (72.37 (9.17) vs. 77.65 (9.19), p = .063) {data not in tables}. It was unclear whether their body composition was due to a GFD, as we did not track their weight status or body composition at diagnosis. In a US cohort study, Reilly et al. (2011) showed that a GFD has a beneficial effect in most overweight children with CD.[32] However, some overweight children worsened their BMI z-scores while compliant with GFD, and noncompliant overweight patients increased their BMI at follow-up. Prospective studies are needed among our CD patients in Kuwait to identify factors related to changes in body composition including physical activity, dietary choices, daily total energy intake, and macronutrient intake.
Our data showed that CD children were eight times more likely to have IDA (OR = 8.00 [1.771–36.135]; p = .007) and 36.4% of cases had IDA. Notably, the prevalence of IDA was much higher than their reported 19.5% (Fig. 1), which indicates their lack of awareness of it. These results agree with those of several studies on pediatric and adult populations.[33, 34] In a multicenter Italian study, which included 1026 patients with subclinical/silent CD, IDA was found in 46% of adults and 35% of pediatric patients.[35] Anemia in children with CD has adverse effects on motor, cognitive, and socioemotional development and alters neuromaturation.[36] It is a relatively frequent condition in CD caused by iron loss and reduced iron absorption, which might be a consequence of the reduced expression of different proteins regulating iron absorption. Even after adopting a GFD, anemia persists because a GFD often lacks a high iron content. Notably, our data showed that adolescent girls had a higher prevalence of IDA than boys in both cases and controls, which might be partly explained by blood loss during menstruation and worse dietary habits compared to boys, as previously reported among Kuwaiti adolescents.[37] A good approach to prevent malnutrition and maintain growth in children with CD is to start a GFD supported by oral administration of iron.[33, 35, 38]
Vitamin B12 deficiency was found in 46.6% of cases with CD, and 15% had megaloblastic anemia. In our study, the prevalence of vitamin B12 deficiency in patients with CD was higher than that in other reports. Dickey et al. showed that circulating levels of vitamin B12 were inadequate in 5–40% of CD children at diagnosis and in 2.9–41% of patients following a GFD.[39] Although the absorption site of vitamin B12 is preserved in patients with CD, its deficiency is still common in this population.[40] Vitamin B12 deficiency in children with CD can lead to developmental delays, weakness, and FTT. Dietitians must promote dietary B12 by increasing the intake of fortified cereals, eggs, animal liver, and kidneys. Numerous studies recommend starting vitamin B12 supplementation to meet these requirements and protect against neurological complications.[40] In addition, a long-term GFD is an effective treatment for normalizing vitamin B12 in CD.[41] Moreover, frequent vitamin B12 screening may be beneficial for reducing the risk of deficiency-related diseases. [42]
Furthermore, vitamin D deficiency was prevalent in 65.3% of our cases and vitamin D insufficiency in 18.7%. CD patients in our study were six times more likely to have vitamin D deficiency (OR = 6.65 [1.91–16.71], p = .002). Rotondi et al. found that vitamin D deficiency is a common feature, reaching up to 52% in CD children at diagnosis.[43] Vitamin D deficiency is an important health problem that can lead to muscle weakness, muscular pain, and rickets in young children. Low sunshine exposure, skin pigmentation, air pollution, skin covering, and low vitamin D intake may be responsible for this deficiency; however, damage to the small intestinal mucosa, especially at first diagnosis, may be a contributing factor. Decreased intestinal absorption of calcium and vitamin D may be due to chronic intestinal inflammation, which may lead to the release of proinflammatory cytokines with a subsequent increase in bone loss. [40, 43] Therefore, CD children on GFD need vitamin D and calcium supplementation to bring the values to the normal range. [40, 43]
Our study found that low socioeconomic status was associated with a higher risk of CD and worsening of anemia, low ferritin and vitamin D levels, and growth stunting, as shown in our multivariate logistic regression models. A high proportion of our CD cases were non-Kuwaitis (42.9% vs. 13.3%, p = 0.004). Non-Kuwaitis captured in this study earn a low income, which may create a gap in health literacy and access to health information, which is often found between socioeconomic brackets, as seen elsewhere.[44] It appears that CD patients who were at a lower socioeconomic status and education level were less inclined to obtain GF products due to their cost.
Despite a high rate of compliance with a GFD, we found a high proportion of children with CD with deficiencies in vitamin D and vitamin B12, low hemoglobin concentrations, and serum ferritin levels. Dietary adherence to a GFD is paramount as it is the only treatment available for CD. GFD is not sufficient to offset poor eating patterns in children with CD, which can lead to malnutrition, obesity, and related chronic diseases. Dietitians can play an important role in children with CD by following up with dietary adherence to GFD, correcting nutritional deficiencies, and preventing the development of possible comorbidities. Studies are needed to identify novel targets for therapy as well as lifestyle and behavioral recommendations to improve patient outcomes and support adherence to GFD. Family based intervention may be a workable strategy for educating patients with CD, supporting adherence to GFD, improving nutritional status, and preventing nutritional deficiency.
Early identification of symptoms may help prevent the delayed diagnosis of CD, which causes severe malnutrition and growth impairment. In addition, increasing awareness among healthcare professionals, including pediatricians and dietitians, about new clinical manifestations and nutritional deficiencies common in CD is essential to provide appropriate and efficacious monitoring strategies and interventions in their care plans. An annual review and follow-up after CD diagnosis, including tests for vitamin D, vitamin B12, folate, CBC, and ferritin, should be performed to screen for possible emerging nutritional deficiencies.[45] Regular follow-up with a dietitian is important for developing healthy dietary habits that prevent malnutrition and obesity. In addition, access to a dietitian may provide the best choices for GF products with high nutritional quality.